Clinical bone marrow transplantation between HLA-matched siblings is often complicated by the development of graft-versus-host (GVH) disease. GVH reactions result from the recognition of foreign minor histocompatibility antigens of the host by T lymphocytes in the bone marrow graft. Little is known about these antigens because there have been no identifying reagents for this study. We have successfully generated cytotoxic T-cell lines from the blood of recipients of HLA-matched marrow grafts. These effectors demonstrate specificity for factors inherited within the family that segregate independently of HLA and are thus identified as minor alloantigens. Such CTL have been generated even from cases in which there was no evident GVHD, nevertheless they may identify minor antigens capable of triggering GVH reactions. Current studies are directed at identifying these minor antigens in the general population. We are seeking antigens that may be of special importance in BMT by virtue of modest frequency, just as those of the ABO system are important in blood transfusion. (TT)